The field of DNA nanotechnology has transformed DNA from a biological material that stores genetic information into a construction material that can be used to build 3-dimensional scaffolds, structures, and devices with nanoscale features (N. C. Seeman, Annu. Rev. Biochem., 2010, 79, 65-87; A. V. Pinheiro, et al., Nat. Nanotechnol. 2011, 6, 763-772). The ability to precisely control the organization of DNA relies on Watson-Crick base pairing, which acts as a molecular glue to hold strands of DNA together in a predictable manner. There are a variety of strategies that can be used to create DNA nanostructures, each that use a combination of different single-stranded (ssDNA) sequences that when mixed together and subjected to specific annealing conditions (i.e., controlled cooling rates, specific ions, and pH) fold together to produce double stranded DNA segments that organize into highly uniform structures of the desired shape (T. Toning, et al., Gothelf, Chem. Soc. Rev., 2011, 40, 5636-5646; C. Lin, et al., ChemPhysChem, 2006, 7, 1641-1647; F. A. Aldaye, et al., Science, 2008, 321, 1795-1799). The predictability of base pairing affords the opportunity to rationally select these ssDNA sequences, often with the aid of software, that can combine together to form tetrahedrons, cages, barrels, and tube structures while maintaining ssDNA overhangs that act as addressable locations and allow the structures to be further functionalized with drugs, dyes, and metals for use as therapeutics, diagnostics, electronics and photonics, and in molecular and cellular biophysical studies (A. V. Pinheiro, et al., Nat. Nanotechnol. 2011, 6, 763-772; F. A. Aldaye, et al., Science, 2008, 321, 1795-1799).
An alternative approach to form DNA nanostructures is to covalently link a hydrophilic ssDNA sequence with a hydrophobic tail (a polymer or other hydrophobic moiety) to form an amphiphilic molecule (e.g., a nucleic acid amphiphile) (M. Kwak, et al., Chem. Soc. Rev., 2011, 40, 5745-5755; A. Patwa, et al., Chem. Soc. Rev., 2011, 40, 5844-5854). The amphiphilic nature of the conjugate induces spontaneous assembly of the molecules when added to an aqueous environment, with the hydrophobic tails preferring to sequester themselves into a hydrophobic domain while the ssDNA sequences extend into the aqueous solution. With this structural arrangement the ssDNA is not required to base pair in order to create the nanostructure and remains available for base pairing with complimentary ssDNA sequences. Additionally, this approach to forming DNA nanostructures does not require base pairing prediction software and reduces the requirements for specific annealing conditions. However, this approach has not yet been used to create nanostructures with similar levels of complexity as those achieved by other approaches like DNA origami and DNA tile assembly (F. A. Aldaye, et al., Science, 2008, 321, 1795-1799). To date, the majority of structures created by ssDNA-amphiphile assembly have been spherical and cylindrical micelles (M. Kwak, et al., Chem. Soc. Rev., 2011, 40, 5745-5755; M.-P. Chien, et al., Angew. Chem. Int. Ed., 2010, 49, 5076-5080).
Another study investigated how an additional building block, a spacer molecule used to link a ssDNA aptamer headgroup and hydrophobic lipid-like tail, could affect ssDNA-amphiphile assembly (T. R. Pearce, et al., Chem. Commun., 2014, 50, 210-212). It was found that globular micelles were formed when a 25 nucleotide aptamer was directly conjugated to a C16 dialkyl tail or conjugated to the tail via hydrophilic PEG4 or PEG8 spacers, but that flat and twisted nanotapes comprised of bilayers of amphiphiles were formed when hydrophobic C12 and C24 spacers were used (T. R. Pearce, et al., Chem. Commun., 2014, 50, 210-212). The nanotape morphology achieved by including a hydrophobic spacer in the design of the amphiphile was not predicted by the standard packing parameter analysis, leading to the hypothesis that polycarbon spacers, through attractive hydrophobic interactions, may force the aptamer headgroups into close proximity of each other, thus reducing the interfacial headgroup area and allowing the nanotapes to form (T. R. Pearce, et al., Chem. Commun., 2014, 50, 210-212). Other studies have shown that amphiphiles created with a 40 nucleotide ssDNA aptamer headgroup containing a large number of guanine nucleotides capable of forming intermolecular parallel G-quadruplexes with neighbouring aptamer headgroups self-assembled into nanotapes in the absence of a polycarbon spacer (B. Waybrant, et al., Langmuir, 2014, DOI: 10.1021/la500403v). This finding suggested that the intermolecular interactions that produced the G-quadruplex structure may have reduced the effective headgroup area of the ssDNA in a manner analogous to the polycarbon spacer and encouraged the assembly of bilayer nanotapes (B. Waybrant, et al., Langmuir, 2014, DOI: 10.1021/la500403v). Thus, the factors that influence assembly of ssDNA-amphiphiles into 3-dimensional structures is complex.
There is an ongoing need for 3-dimensional structures with nano-scale features (e.g., nanotubes, twisted nanotapes or helical nanotapes) including ones that are based on nucleic acid amphiphiles (e.g., ssDNA amphiphiles). There is also a need for 3-dimensional structures with nano-scale features (e.g., nanotubes, twisted nanotapes or helical nanotapes formed from ssDNA amphiphiles) that can be used, for example, to deliver therapeutic agents and/or target certain biological molecules and/or detect certain proteins or as templates for the design and engineering of other materials.